Mechanobiology describes the relationship between a cell and its environment; how a cell can detect, measure and respond to the rigidity of its substrate and how these processes apply to larger biological systems.

The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. Learn More

Cell membranes are highly enriched in signaling receptors, transmembrane mechanosensors, pumps and channels, and, depending on their makeup, can recruit and retain a pool of mechanosensors important in the field of mechanobiology. Learn More

The detection of mechanical signals, and their integration into biochemical pathways, is integral to the cell’s ability to sense, measure and respond to its physical surroundings. Mechanosignl and enable communication between neighbouring cells. Learn More

Genome regulation encompasses all facets of gene expression, from the biochemical modifications of DNA, to the physical arrangement of chromosomes and the activity of the transcription machinery. Learn More

Development in higher order organisms commences at conception and continues into old age. In the earliest stages of development, the physical properties of the microenvironment can direct cell differentiation, and initiate the coordinated movement of groups of cells to establish the patterns that will define how the body is arranged. Learn More

Insights into disease etiology and progression, the two major aspects of pathogenesis, are paramount in the prevention, management and treatment of various diseases. While many people will be genetically predisposed to a given disease, the mechanical properties of the tissue or cellular environment can also contribute to disease progression or its onset.Learn More

What is chromatin, heterochromatin and euchromatin?steve2018-05-21T15:19:37+08:30

What is chromatin, heterochromatin and euchromatin?

The human genome contains over 3 billion base pairs or nucleotides. These nucleotides, which are arranged in a linear sequence along DNA (deoxyribonucleic acid), encode every protein and genetic trait in the human body. This information is contained in approximately 20,000 genes which, surprisingly, represent only a small fraction (about 1.5%) of the total DNA. The remainder is comprised of non-coding sequences. The integrity of the genetic sequence is essential for normal cell function and this is highlighted when genetic anomalies go undetected by intrinsic genetic repair mechanisms and give rise to dysfunctional proteins and various diseases states.

In the interphase nucleus, chromosomes are difficult to distinguish from each other. Never the less, they do occupy a discrete space inside a nucleus – so called chromosome territory (borders of chromosomes territories are suggested as red dotted lines in the figure A). Lighter stained euchromatin (transcriptionally active) and the patches of darker heterochromatin (transcriptionally silent) are, on the other hand, easy to visualize. During the cell division, chromosome territories transform into highly condensed chromosomes, which then can be clearly distinguished from one another. Together, mitotic chromosomes, visualized in light microscope, are called karyotype.

A series of processes must therefore take place that enable the cell to package DNA within the confines of the nucleus whilst retaining its ability to transcribe and duplicate the entire DNA sequence and maintain its integrity. This is achieved through an elaborate process of DNA condensation that sees DNA packaged into 46 chromosomes (or 23 chromosome pairs) in humans. The number of chromosomes varies from species to species; for example, there are 40 chromosomes (20 pairs) in mice, 8 chromosomes (4 pairs) in the common fruit fly and 10 chromosomes (5 pairs) in the Arabidopsis thaliana plant.

Chromosomes reach their highest level of condensation during cell division, or mitosis, where they will acquire a discrete 4-armed or 2-armed morphology that represents approximately 10,000-fold compaction. Although this heavily condensed mitotic form has become the most common way of depicting chromosomes, their structure is significantly different during the interphase. Compared to mitotic chromosomes, interphase chromosomes are less condensed and occupy the entire nuclear space, making them somewhat difficult to distinguish.

Like the formation of metaphase chromosomes, the compaction required to fit a full set of interphase chromosomes into the nucleus is achieved through a series of DNA folding, wrapping and bending events that are facilitated by histones, which are highly conserved basic nuclear proteins that enable DNA compaction by neutralizing DNA’s negative charge. Histones generally arrange as an octamer in complex with DNA to form the nucleosome.The combination of DNA and histone proteins that make up the nuclear content is often referred to as chromatin.

Heterochromatin vs Euchromatin

Traditionally, interphase chromatin is classified as either euchromatin or heterochromatin, depending on its level of compaction. Euchromatin has a less compact structure, and is often described as a 11 nm fiber that has the appearance of ‘beads on a string’ where the beads represent nucleosomes and the string represents DNA. In contrast, heterochromatin is more compact, and is often reported as being composed of a nucleosome array condensed into a 30 nm fiber. It should be noted, however, that the 30 nm fiber has never been visualized in vivo, and its existence is questionable.

Euchromatin has a less compact structure, whereas heterochromatin is more compact and composed of an array of nucleosomes condensed into a fiber. These levels of chromatin compaction are illustrated here in two chromosomes (orange and blue).

With DNA encoding the genetic information of the cell, the condensation of this molecule is obviously more complicated than can be represented by simple 11 nm or 30 nm fiber models. The transcription machinery requires access to the genetic information throughout the cell cycle, while replication machinery will copy the DNA during S-phase. This added complexity is evident in key differences between euchromatin and heterochromatin, and also in the localization of chromatin within the nucleus.

The fact that intrinsic mechanisms exist in the condensation of DNA to control access for transcriptional or replication purposes is reflected in the presence of repetitive DNA elements such as satellite sequences, as well as transposable elements within heterochromatin, particularly in the highly condensed centromeres and telomeres. These regions, which are known as constitutive heterochromatin, remain condensed throughout the cell cycle and are not actively transcribed. Facultative heterochromatin, which can be unwound to form euchromatin, on the other hand, is more dynamic in nature and can form and change in response to cellular signals and gene activity [1]. This region often contains genetic information that will be transcribed during the cell cycle.

More Questions FAQ

A series of processes must take place that enable the cell to package DNA within the confines of the nucleus whilst retaining its ability to transcribe and duplicate the entire DNA sequence and maintain its integrity. This is achieved through an elaborate process of DNA condensation that sees DNA packaged into 46 chromosomes (or 23 chromosome pairs) in humans. Read more..

The final step in translation is ribosome recycling, which sees the ribosome split into its smaller subunit parts and prepare for another round of translation. In eukaryotes this means the 80S ribosome splits into its 40S and 60S subunits. Read more..

What happens during the elongation stage of translation?Sruthi Jagannathan2017-12-19T16:46:46+08:30

Elongation occurs over several well-defined steps, beginning with the recognition of the mRNA codons by their corresponding aminoacyl-tRNA. Association with the mRNA occurs via the ribosomal A site and is influenced by various elongation factors. Read more..

The first step in translation is known as initiation. Here, the large (60S) and small (40S) ribosomal units are assembled into a fully functional 80S ribosome. This is positioned at the start codon (AUG) of the mRNA strand to be translated. Read more..

Traditionally, chromatin is classified as either euchromatin or heterochromatin, depending on its level of compaction. Euchromatin has a less compact structure, and is often described as a 11 nm fiber that has the appearance of ‘beads on a string’ where the beads represent nucleosomes and the string represents DNA. In contrast, heterochromatin is more compact, and is often reported as being composed of a nucleosome array condensed into a 30 nm fiber. Read more..

Despite 20,000 genes being present in each haploid nucleus, the number of transcription foci is limited to around 2000. These transcription foci, also known as transcriptional factories are distinct submicron nuclear regions that are associated with nascent RNA production and are enriched in RNA polymerase II (RNA pol II) complexes. Read more..

With the development of high-throughput biochemical techniques, such as 3C (‘chromosome conformation capture’) and 4C (‘chromosome conformation capture-on-chip’ and ‘circular chromosome conformation capture’), numerous spatial interactions between neighbouring chromatin territories have been described. Together, these observations and physical simulations have led to the proposal of various models that aim to define the structural organization of chromosome territories. Read more..

As an integral part of cellular behavior, cells are sensitive to matrix rigidity, local geometry and stress or strain applied by external factors. In recent years, it has been established that an extensive network of protein assembly couples the cytoskeleton to the nucleus and that condensation forces of the chromatin balance cytoskeletal forces resulting in a prestressed nuclear organization. Read more..

Cells must replicate their DNA before they can divide. This ensures that each daughter cell gets a copy of the genome, and therefore, successful inheritance of genetic traits. DNA replication is an essential process and the basic mechanism is conserved in all organisms. Read more..

While chromosome territory dynamics is believed to regulate gene expression through the redistribution of genes and the subsequent co-localization of these genes with transcription machinery, changes are also commonly made to the chromosome structure at a ‘local’ level. Although these changes do not necessarily involve the redistribution of genes, they do have a significant influence on gene regulation. Read more..

The spatial organization of chromatin within the 3-dimensional space of a chromosome territory enables the co-localization of co-transcribed genes and their transcriptional foci. Many gene positioning studies have shown that individual genes often loop out of their chromosomal territory to co-localize with transcription factories. Read more..

What is the chromatin polymer model of chromosome territory organization?steve2018-01-19T15:08:09+08:30

The chromatin polymer models assume a broad range of chromatin loop sizes and predict the observed distances between genomic loci and chromosome territories, as well as the probabilities of contacts being formed between given loci. These models apply physics-based approaches that highlight the importance of entropy for understanding nuclear organization… Read more…

What is the Fraser and Bickmore model of chromosome territory organization?steve2018-01-19T15:06:27+08:30

The Fraser and Bickmore model emphasizes the functional importance of giant chromatin loops, which originate from chromosome territories and expand across the nuclear space in order to share transcription factories. In this case, both cis- and trans- loops of decondensed chromatin can be co-expressed and co-regulated by the same transcription factory… Read more…

What is the interchromatin network (ICN) model of chromosome territory organization?steve2018-01-19T15:12:33+08:30

The interchromatin network (ICN) model of chromosome territory organization predicts that intermingling chromatin fibers/loops can make both cis- (within the same chromosome) and trans- (between different chromosomes) contacts. This intermingling is uniform and makes distinction between the chromosome territory and interchromatin compartment functionally meaningless… Read more…

With the development of high-throughput biochemical techniques, such as 3C (‘chromosome conformation capture’) and 4C (‘chromosome conformation capture-on-chip’ and ‘circular chromosome conformation capture’), numerous spatial interactions between neighbouring chromatin territories have been described. These descriptions have been supplemented with the construction of spatial proximity maps for the entire genome (e.g., for a human lymphoblastoid cell line). Together, these observations and physical simulations have led to the proposal of various models that aim to define the structural organization of chromosome territories… Read more…

During interphase, each chromosome occupies a spatially limited, roughly elliptical domain which is known as a chromosome territory (CT). Each chromosome territory is comprised of higher order chromatin units of ~1 Mb each. These units are likely built up from smaller loop domains. Read more..

In order to fit DNA into the nucleus, it must be packaged into a highly compacted structure known as chromatin. In the first step of this process DNA is condensed into a 11 nm fiber that represents an approximate 6-fold level of compaction. This is achieved through nucleosome assembly. Read more..

A series of processes must take place that enable the cell to package DNA within the confines of the nucleus whilst retaining its ability to transcribe and duplicate the entire DNA sequence and maintain its integrity. This is achieved through an elaborate process of DNA condensation that sees DNA packaged into 46 chromosomes (or 23 chromosome pairs) in humans. Read more..

The human genome contains over 3 billion base pairs or nucleotides. These nucleotides, which are arranged in a linear sequence along DNA (deoxyribonucleic acid), encode every protein and genetic trait in the human body… Read more…

How does the cytoskeleton influence nuclear morphology and positioning?steve2018-01-19T16:12:40+08:30

Work by Mazumder et al. ascertained the active involvement of cytoskeletal forces in determining nuclear morphology. Change in nuclear size upon perturbation of actomyosin and microtubules affirmed their roles in exerting tensile and compressive forces respectively on the nucleus, correlating with their functions in the cellular context , … Read more…

How does the cytoskeleton couple the plasma membrane to the nucleus?steve2018-01-19T16:24:16+08:30

Cytoskeletal filaments bridge the nucleus to the plasma membrane, which in turn is anchored at sub-cellular sites to extracellular substrates via a plethora of proteins that form focal adhesions (FAs). FAs are points of cross-talk between transmembrane integrin receptors and the cytoplasmic filaments and thus are key sites for both biochemical and mechanotransduction pathways… Read more…

How is the organization and function of the genome regulated?steve2017-12-18T14:43:41+08:30

Genome regulation encompasses all facets of gene expression, from the biochemical modifications of DNA, to the physical arrangement of chromosomes and the activity of the transcription machinery.The genome regulation programs that cells engage control which proteins are produced, and to what level. The programs are established during stem cell differentiation, and therefore dictate the specialized functions that the cell will carry out throughout its lifetime… Read more…

What are intermediate chromatin structures?Andrew Wong2017-12-19T15:02:43+08:30

Despite the extensive knowledge already gained on the structure of the 11 nm nucleosome fiber, as well as metaphase chromosomes, the intermediate chromatin structures commonly described are largely hypothetical and yet to be observed in vivo.Two popular models that were proposed based on in vitro data are the solenoid and zigzag. Read more..